Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites

Authors

  • Joan Clària,

    1. DNA Unit, Hospital Clínic, Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Jeffrey D. Kent,

    1. Pfizer Inc., Skokie, IL
    Search for more papers by this author
  • Marta López-Parra,

    1. DNA Unit, Hospital Clínic, Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Ginés Escolar,

    1. Hemotherapy and Hemostasis Laboratory, Hospital Clínic, Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Luís Ruiz-del-Arbol,

    1. Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain
    Search for more papers by this author
  • Pere Ginès,

    1. Liver Unit-Institut de Malalties Digestives, Hospital Clínic, Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Wladimiro Jiménez,

    1. Hormonal Laboratory, Hospital Clínic, Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Boris Vucelic,

    1. Department of Gastroenterology, Clinical Hospital Center Rebro, Zagreb, Croatia
    Search for more papers by this author
  • Vicente Arroyo

    Corresponding author
    1. Liver Unit-Institut de Malalties Digestives, Hospital Clínic, Institut d′Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
    • Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain
    Search for more papers by this author
    • fax: (34) 93-227-5454.


  • Conflict of interest: Nothing to report.

Abstract

Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 ± 27 to 84 ± 22 mL/min), renal plasma flow (592 ± 158 to 429 ± 106 mL/min) and urinary prostaglandin E2 excretion (3430 ± 430 to 2068 ± 549 pg/min) and suppression of the diuretic (urine volume: 561 ± 128 to 414 ± 107 mL/h) and natriuretic (urine sodium: 53 ± 13 to 34 ± 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% ± 8% to 47% ± 8%, P < .05) and thromboxane B2 production (41 ± 12 to 14 ± 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis. (HEPATOLOGY 2005;41:579–587.)

Ancillary